DOCK8 immunodeficiency syndrome

DOCK8 immunodeficiency syndrome is a rare genetic immune system disorder characterized by severe, recurrent infections, elevated IgE levels, and an increased risk of cancer. This condition is caused by mutations in the DOCK8 gene and is inherited in an autosomal recessive pattern.

Overview

DOCK8 immunodeficiency syndrome is a disorder of the immune system. The condition is characterized by recurrent infections that are severe and can be life-threatening. These infections can be caused by bacteria, viruses, or fungi.

This condition is also commonly called autosomal recessive hyper-IgE syndrome. However, researchers have identified several conditions that feature elevated levels of IgE and follow an autosomal recessive pattern of inheritance. Each of these conditions has its own set of additional signs and symptoms and a different genetic cause. Some doctors consider these conditions forms of hyper-IgE syndrome, while others consider them independent disorders.

Symptoms and Clinical Features

People with DOCK8 immunodeficiency syndrome experience a wide range of immune system-related problems and other medical complications:

• Skin Infections: Infections that cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling.
• Respiratory Infections: Frequent bouts of pneumonia and other respiratory tract infections.
• Allergic and Inflammatory Disorders: An inflammatory skin disorder, food or environmental allergies, and asthma.
• Elevated IgE Levels: Abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood, which can be more than 10 times higher than normal for no known reason.
• Hypereosinophilia: Highly elevated numbers of certain white blood cells called eosinophils, which aid in the immune response and are involved in allergic reactions.
• Neurological Problems: Paralysis that affects the face or one side of the body (hemiplegia). Blockage of blood flow in the brain or abnormal bleeding in the brain can also occur, both of which can lead to stroke.
• Increased Cancer Risk: A greater-than-average risk of developing cancer, particularly cancers of the blood or skin.

Frequency

DOCK8 immunodeficiency syndrome is a rare disorder whose prevalence is unknown.

Causes & Genetic Factors

DOCK8 immunodeficiency syndrome is caused by mutations in the DOCK8 gene. The protein produced from this gene plays a critical role in the survival and function of several types of immune system cells.

One of the functions of the DOCK8 protein is to help maintain the structure and integrity of immune cells called T cells and NK cells, which recognize and attack foreign invaders, particularly as these cells travel to sites of infection within the body. In addition, the DOCK8 protein is involved in chemical signaling pathways that stimulate other immune cells called B cells to mature and produce antibodies, which are specialized proteins that attach to foreign particles and germs, marking them for destruction.

Gene mutations result in the production of little or no functional DOCK8 protein. A shortage of this protein impairs normal immune cell development and function:

• T cells and NK cells lacking DOCK8 protein are abnormal and die too easily, particularly when moving through the layers of skin. This impairs the immune response to foreign invaders, accounting for the severe skin infections common in this syndrome.
• A lack of DOCK8 protein impairs B cell maturation and antibody production, leading to recurrent respiratory tract infections.
• It remains unclear how these mutations are involved in other features of the disorder, such as elevated IgE levels and neurological problems.

Associated Gene

• DOCK8

Inheritance Pattern

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Other Names for This Condition

• AR-HIES
• Autosomal recessive HIES
• Autosomal recessive hyper-IgE syndrome
• CID due to DOCK8 deficiency
• Combined immunodeficiency due to DOCK8 deficiency
• DOCK8 deficiency
• Hyper IgE recurrent infection syndrome, autosomal recessive
• Hyper immunoglobulin E syndrome, autosomal recessive
• Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive
• Hyperimmunoglobulin E syndrome type 2
• Non-skeletal hyper-IgE syndrome